Trial Outcomes & Findings for Comparison of Efficacy and Safety of TachoSil® Versus Surgicel® Original for the Secondary Hemostatic Treatment of Needle Hole Bleeding in Vascular Surgery (NCT NCT01500135)

Last Updated: 2017-02-08

Results Overview

After application of Investigational Medicinal Product (IMP) light pressure was applied to the IMP with e.g. gauze pads. The first assessment of hemostasis was at minute 3: the pressure was carefully relieved, and the area was observed for visual bleeding at the site of the IMP. If no bleeding was visible, hemostasis was obtained and recorded.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

150 participants

Primary outcome timeframe

Within 3 minutes

Results posted on

2017-02-08

Participant Flow

Participants took part in the study at 23 investigative sites in the United States from 09 March 2012 to 16 December 2015.

Participants who were elected for planned or subacute vascular surgery were enrolled in a 2:1 ratio to treatment groups: TachoSil® or Surgicel® Original.

Participant milestones

Participant milestones
Measure	TachoSil® TachoSil® absorbable patches, applied topically, once, intraoperatively to stop bleeding. The patches were lightly compressed against the suture line for 3 minutes. The number of patches used was determined by the surgeon based on the size of the wound. If bleeding did not stop after 5 minutes treatment was repeated.	Surgicel® Original Surgicel® Original absorbable patches, applied topically, once, intraoperatively to stop bleeding. The patches were lightly compressed against the suture line for 3 minutes. The number of patches used was determined by the surgeon based on the size of the wound. If bleeding did not stop after 5 minutes treatment was repeated.
Overall Study STARTED	100	50
Overall Study COMPLETED	83	39
Overall Study NOT COMPLETED	17	11

Reasons for withdrawal

Reasons for withdrawal
Measure	TachoSil® TachoSil® absorbable patches, applied topically, once, intraoperatively to stop bleeding. The patches were lightly compressed against the suture line for 3 minutes. The number of patches used was determined by the surgeon based on the size of the wound. If bleeding did not stop after 5 minutes treatment was repeated.	Surgicel® Original Surgicel® Original absorbable patches, applied topically, once, intraoperatively to stop bleeding. The patches were lightly compressed against the suture line for 3 minutes. The number of patches used was determined by the surgeon based on the size of the wound. If bleeding did not stop after 5 minutes treatment was repeated.
Overall Study Withdrawal of Consent	4	0
Overall Study Lost to Follow-up	6	4
Overall Study Fatal Adverse Event (AE)	5	5
Overall Study Principal Investigator (PI) Discretion	1	0
Overall Study Patient Missed Scheduled Appointments	0	1
Overall Study Participant was a Safety Concern	1	0
Overall Study Patient Unable to Make Follow-up Visit	0	1

Baseline Characteristics

Baseline height data is not available for 1 participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TachoSil® n=100 Participants TachoSil® absorbable patches, applied topically, once, intraoperatively to stop bleeding. The patches were lightly compressed against the suture line for 3 minutes. The number of patches used was determined by the surgeon based on the size of the wound. If bleeding did not stop after 5 minutes treatment was repeated.	Surgicel® Original n=50 Participants Surgicel® Original absorbable patches, applied topically, once, intraoperatively to stop bleeding. The patches were lightly compressed against the suture line for 3 minutes. The number of patches used was determined by the surgeon based on the size of the wound. If bleeding did not stop after 5 minutes treatment was repeated.	Total n=150 Participants Total of all reporting groups
Age, Continuous	65.9 years STANDARD_DEVIATION 10.25 • n=100 Participants	67.6 years STANDARD_DEVIATION 12.87 • n=50 Participants	66.5 years STANDARD_DEVIATION 11.18 • n=150 Participants
Age, Customized ≤65 years	48 participants n=100 Participants	22 participants n=50 Participants	70 participants n=150 Participants
Age, Customized >65 years	52 participants n=100 Participants	28 participants n=50 Participants	80 participants n=150 Participants
Gender Female	33 Participants n=100 Participants	26 Participants n=50 Participants	59 Participants n=150 Participants
Gender Male	67 Participants n=100 Participants	24 Participants n=50 Participants	91 Participants n=150 Participants
Race/Ethnicity, Customized White/Caucasian	79 participants n=100 Participants	34 participants n=50 Participants	113 participants n=150 Participants
Race/Ethnicity, Customized Asian	0 participants n=100 Participants	1 participants n=50 Participants	1 participants n=150 Participants
Race/Ethnicity, Customized Black or African American	21 participants n=100 Participants	10 participants n=50 Participants	31 participants n=150 Participants
Race/Ethnicity, Customized Other	0 participants n=100 Participants	4 participants n=50 Participants	4 participants n=150 Participants
Race/Ethnicity, Customized Missing	0 participants n=100 Participants	1 participants n=50 Participants	1 participants n=150 Participants
Race/Ethnicity, Customized Hispanic or Latino	4 participants n=100 Participants	6 participants n=50 Participants	10 participants n=150 Participants
Race/Ethnicity, Customized Non-Hispanic or Latino	95 participants n=100 Participants	42 participants n=50 Participants	137 participants n=150 Participants
Race/Ethnicity, Customized Unknown	1 participants n=100 Participants	1 participants n=50 Participants	2 participants n=150 Participants
Region of Enrollment United States	100 participants n=100 Participants	50 participants n=50 Participants	150 participants n=150 Participants
Height	171.70 cm STANDARD_DEVIATION 10.197 • n=99 Participants • Baseline height data is not available for 1 participant.	166.85 cm STANDARD_DEVIATION 10.381 • n=50 Participants • Baseline height data is not available for 1 participant.	170.07 cm STANDARD_DEVIATION 10.479 • n=149 Participants • Baseline height data is not available for 1 participant.
Weight	81.15 kg STANDARD_DEVIATION 18.738 • n=99 Participants • Baseline weight data is not available for 1 participant.	76.20 kg STANDARD_DEVIATION 21.935 • n=50 Participants • Baseline weight data is not available for 1 participant.	79.49 kg STANDARD_DEVIATION 19.932 • n=149 Participants • Baseline weight data is not available for 1 participant.
Body Mass Index (BMI)	27.45 kg/m^2 STANDARD_DEVIATION 5.702 • n=99 Participants • Baseline BMI data is not available for 1 participant.	27.13 kg/m^2 STANDARD_DEVIATION 6.246 • n=50 Participants • Baseline BMI data is not available for 1 participant.	27.34 kg/m^2 STANDARD_DEVIATION 5.871 • n=149 Participants • Baseline BMI data is not available for 1 participant.
Fertility Status Menstrual	2 participants n=100 Participants	1 participants n=50 Participants	3 participants n=150 Participants
Fertility Status Postmenstrual	15 participants n=100 Participants	15 participants n=50 Participants	30 participants n=150 Participants
Fertility Status Surgically Sterile	16 participants n=100 Participants	10 participants n=50 Participants	26 participants n=150 Participants
Fertility Status Not Applicable	67 participants n=100 Participants	24 participants n=50 Participants	91 participants n=150 Participants

PRIMARY outcome

Timeframe: Within 3 minutes

Population: Full Analysis Set (FAS) included all randomized participants. The endpoint for one participant on TachoSil® was missing; it was assumed that hemostasis was not reached within 3 minutes.

Outcome measures

Outcome measures
Measure	TachoSil® n=100 Participants TachoSil® absorbable patches, applied topically, once, intraoperatively to stop bleeding. The patches were lightly compressed against the suture line for 3 minutes. The number of patches used was determined by the surgeon based on the size of the wound. If bleeding did not stop after 5 minutes treatment was repeated.	Surgicel® Original n=50 Participants Surgicel® Original absorbable patches, applied topically, once, intraoperatively to stop bleeding. The patches were lightly compressed against the suture line for 3 minutes. The number of patches used was determined by the surgeon based on the size of the wound. If bleeding did not stop after 5 minutes treatment was repeated.
Percentage of Participants With Intra-operative Hemostasis at the Evaluation Site Within 3 Minutes After Application of the Randomized Treatment	26.0 percentage of participants Interval 17.7 to 35.7	18.0 percentage of participants Interval 8.6 to 31.4

SECONDARY outcome

Timeframe: Within 5 minutes

Population: FAS included all randomized participants. The endpoint for one participant on TachoSil® was missing; it was assumed that hemostasis was not reached within 5 minutes.

After application of Investigational Medicinal Product (IMP) light pressure was applied to the IMP with e.g. gauze pads. If hemostasis was not obtained at minute 3, pressure was immediately reapplied. Hemostasis was re-assessed at minutes 4 and 5.

Outcome measures

Outcome measures
Measure	TachoSil® n=100 Participants TachoSil® absorbable patches, applied topically, once, intraoperatively to stop bleeding. The patches were lightly compressed against the suture line for 3 minutes. The number of patches used was determined by the surgeon based on the size of the wound. If bleeding did not stop after 5 minutes treatment was repeated.	Surgicel® Original n=50 Participants Surgicel® Original absorbable patches, applied topically, once, intraoperatively to stop bleeding. The patches were lightly compressed against the suture line for 3 minutes. The number of patches used was determined by the surgeon based on the size of the wound. If bleeding did not stop after 5 minutes treatment was repeated.
Percentage of Participants With Intra-operative Hemostasis at the Evaluation Site Within 5 Minutes After Application of the Randomized Treatment	39.0 percentage of participants Interval 29.4 to 49.3	42.0 percentage of participants Interval 28.2 to 56.8

SECONDARY outcome

Timeframe: Within 10 minutes

Population: FAS included all randomized participants. Participants who did not achieve hemostasis by 10 minutes were censored.

After application of Investigational Medicinal Product (IMP) light pressure was applied to the IMP with e.g. gauze pads. Hemostasis was assessed at 3, 4, and 5 minutes. If hemostasis was not obtained after 5 minutes a second application of IMP was applied with 3 minutes of light pressure and hemostasis was re-assessed at 8, 9 and 10 minutes.

Outcome measures

Outcome measures
Measure	TachoSil® n=100 Participants TachoSil® absorbable patches, applied topically, once, intraoperatively to stop bleeding. The patches were lightly compressed against the suture line for 3 minutes. The number of patches used was determined by the surgeon based on the size of the wound. If bleeding did not stop after 5 minutes treatment was repeated.	Surgicel® Original n=50 Participants Surgicel® Original absorbable patches, applied topically, once, intraoperatively to stop bleeding. The patches were lightly compressed against the suture line for 3 minutes. The number of patches used was determined by the surgeon based on the size of the wound. If bleeding did not stop after 5 minutes treatment was repeated.
Time to Intra-operative Hemostasis Within 10 Minutes at the Evaluation Site After Application of the Randomized Treatment	8.0 minutes 95% Confidence Interval 18.87 • Interval 8.0 to 9.0	8.0 minutes 95% Confidence Interval 14.63 • Interval 5.0 to 10.0

Adverse Events

TachoSil®

Serious events: 49 serious events

Other events: 52 other events

Deaths: 0 deaths

Surgicel® Original

Serious events: 19 serious events

Other events: 28 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Publication restrictions are in place

Restriction type: OTHER

Measure	TachoSil® n=99 participants at risk TachoSil® absorbable patches, applied topically, once, intraoperatively to stop bleeding. The patches were lightly compressed against the suture line for 3 minutes. The number of patches used was determined by the surgeon based on the size of the wound. If bleeding did not stop after 5 minutes treatment was repeated.	Surgicel® Original n=50 participants at risk Surgicel® Original absorbable patches, applied topically, once, intraoperatively to stop bleeding. The patches were lightly compressed against the suture line for 3 minutes. The number of patches used was determined by the surgeon based on the size of the wound. If bleeding did not stop after 5 minutes treatment was repeated.
Infections and infestations Urinary tract infection	9.1% 9/99 • From the signing of informed consent to the follow-up visit (Up to 6 Months) Safety Population included all randomized participants who received treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.0% 4/50 • From the signing of informed consent to the follow-up visit (Up to 6 Months) Safety Population included all randomized participants who received treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Seroma	3.0% 3/99 • From the signing of informed consent to the follow-up visit (Up to 6 Months) Safety Population included all randomized participants who received treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.0% 4/50 • From the signing of informed consent to the follow-up visit (Up to 6 Months) Safety Population included all randomized participants who received treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Wound dehiscence	3.0% 3/99 • From the signing of informed consent to the follow-up visit (Up to 6 Months) Safety Population included all randomized participants who received treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	12.0% 6/50 • From the signing of informed consent to the follow-up visit (Up to 6 Months) Safety Population included all randomized participants who received treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Blood and lymphatic system disorders Anaemia	14.1% 14/99 • From the signing of informed consent to the follow-up visit (Up to 6 Months) Safety Population included all randomized participants who received treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	12.0% 6/50 • From the signing of informed consent to the follow-up visit (Up to 6 Months) Safety Population included all randomized participants who received treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Cardiac disorders Atrial fibrillation	5.1% 5/99 • From the signing of informed consent to the follow-up visit (Up to 6 Months) Safety Population included all randomized participants who received treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/50 • From the signing of informed consent to the follow-up visit (Up to 6 Months) Safety Population included all randomized participants who received treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Constipation	11.1% 11/99 • From the signing of informed consent to the follow-up visit (Up to 6 Months) Safety Population included all randomized participants who received treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	10.0% 5/50 • From the signing of informed consent to the follow-up visit (Up to 6 Months) Safety Population included all randomized participants who received treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Nausea	7.1% 7/99 • From the signing of informed consent to the follow-up visit (Up to 6 Months) Safety Population included all randomized participants who received treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/50 • From the signing of informed consent to the follow-up visit (Up to 6 Months) Safety Population included all randomized participants who received treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Oedema peripheral	10.1% 10/99 • From the signing of informed consent to the follow-up visit (Up to 6 Months) Safety Population included all randomized participants who received treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/50 • From the signing of informed consent to the follow-up visit (Up to 6 Months) Safety Population included all randomized participants who received treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Peripheral swelling	3.0% 3/99 • From the signing of informed consent to the follow-up visit (Up to 6 Months) Safety Population included all randomized participants who received treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.0% 3/50 • From the signing of informed consent to the follow-up visit (Up to 6 Months) Safety Population included all randomized participants who received treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Hypomagnesaemia	7.1% 7/99 • From the signing of informed consent to the follow-up visit (Up to 6 Months) Safety Population included all randomized participants who received treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	10.0% 5/50 • From the signing of informed consent to the follow-up visit (Up to 6 Months) Safety Population included all randomized participants who received treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Hypokalaemia	6.1% 6/99 • From the signing of informed consent to the follow-up visit (Up to 6 Months) Safety Population included all randomized participants who received treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	10.0% 5/50 • From the signing of informed consent to the follow-up visit (Up to 6 Months) Safety Population included all randomized participants who received treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Pain in extremity	9.1% 9/99 • From the signing of informed consent to the follow-up visit (Up to 6 Months) Safety Population included all randomized participants who received treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.0% 3/50 • From the signing of informed consent to the follow-up visit (Up to 6 Months) Safety Population included all randomized participants who received treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Psychiatric disorders Insomnia	0.00% 0/99 • From the signing of informed consent to the follow-up visit (Up to 6 Months) Safety Population included all randomized participants who received treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.0% 3/50 • From the signing of informed consent to the follow-up visit (Up to 6 Months) Safety Population included all randomized participants who received treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Renal and urinary disorders Urinary retention	3.0% 3/99 • From the signing of informed consent to the follow-up visit (Up to 6 Months) Safety Population included all randomized participants who received treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	12.0% 6/50 • From the signing of informed consent to the follow-up visit (Up to 6 Months) Safety Population included all randomized participants who received treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Vascular disorders Hypotension	11.1% 11/99 • From the signing of informed consent to the follow-up visit (Up to 6 Months) Safety Population included all randomized participants who received treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	10.0% 5/50 • From the signing of informed consent to the follow-up visit (Up to 6 Months) Safety Population included all randomized participants who received treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Vascular disorders Hypertension	5.1% 5/99 • From the signing of informed consent to the follow-up visit (Up to 6 Months) Safety Population included all randomized participants who received treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.0% 2/50 • From the signing of informed consent to the follow-up visit (Up to 6 Months) Safety Population included all randomized participants who received treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.